Pain is the most common symptom for which patients seek medical advice and treatment. Pain can be acute or chronic. While acute pain is usually self-limited, chronic pain can persist for 3 months or longer and lead to significant changes in a patient's personality, lifestyle, functional ability or overall quality of life (K. M. Foley, Pain, in Cecil Textbook of Medicine 100-107, J. C. Bennett and F. Plum eds., 20th ed. 1996).
Pain has been traditionally managed by administering a non-opioid analgesic, including but not limited to acetylsalicyclic acid, choline magnesium trisalicylate, acetaminophen, ibuprofen, fenoprofen, diflusinal and naproxen; or an opioid analgesic, including but not limited to morphine, hydromorphone, methadone, levorphanol, fentanyl, oxycodone and oxymorphone. Id.
U.S. Pat. Nos. 6,576,650 6,166,039 and 5,849,761 to Yaksh, and U.S. Pat. No. 6,573,282, to Yaksh et al., describe 1,4-substituted piperidine derivatives for use as peripherally acting anti-hyperalgesic opiates.
U.S. Pat. No. 6,362,203 B1 to Mogi et al. describes 4-hydroxy-4-phenylpiperidine derivatives that have peripheral analgesic action.
Canadian Patent Publication No. 949560 of Carron et al. describes piperidine derivatives for use as analgesics.
International PCT Publication WO 02/38185 A2 by Dunn et al. describes 1,4-substituted piperidine compounds for use as anti-hyperalgesic opiates.
International PCT Publication WO 01/70689 A1 describes piperidine derivatives for use as opioid δ receptor agonists.
Traditional opioid analgesics exert their pharmacological activity once they have passed through the blood-brain barrier (BBB). But passage through the BBB can lead to undesirable central nervous system (CNS)-mediated side effects, such as respiratory depression, increased drug tolerance, increased drug dependence, constipation and unwanted euphoria.
There remains a continuing need for new drugs that can be used to treat or prevent pain, and that reduce or avoid one or more side effects associated with traditional therapy.